This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Our general objective is to enable the application of vibrational spectroscopy to cancer diagnosis and treatment monitoring. The detection of cancer at its earliest stages is crucial, for it greatly improves the likelihood of successful treatment. Traditional methods of diagnosis have relied on physical removal of a portion of tissue and microscopic assessment of morphology. The need for tissue removal reduces the area of tissue that can be sampled. A noninvasive technique would eliminate this problem. Furthermore, a noninvasive technique has the potential to allow treatment to begin during the same endoscopic procedure used for diagnosis and reduce other complications associated with tissue removal such as tissue handling and increased risk of infection to the patient. We will focus on developing Raman spectroscopy for detection of precancerous conditions in patients with Barrett's esophagus. Barrett's esophagus is a pathology in which the squamous epithelial lining is replaced by a specialized metaplastic epithelium and the likelihood of adenocarcinoma is increased. Because the microscopic changes of dysplasia are difficult to observe, the entire area of metaplastic epithelium should be sampled. Therefore, Barrett's esophagus is well-suited for a noninvasive diagnostic technique. The methods and techniques developed in this proposal may also find application in other tissues such as the cervix. The second goal of our work is to develop Raman spectroscopy as a method for assessing the effects of treatment. Current methods for monitoring the response of an individual tumor to therapy are unreliable and often difficult to implement during the course of therapy. Development of noninvasive or minimally-invasive optical methods to reliably identify regions of apoptosis and necrosis would provide a simple method for assaying tumor response in each individual cancer patient. Consequently, treatments could be customized.